Anxiety and mood disorders co-occur at levels far greater than chance and are considerably more severe, persistent, and disabling in the comorbid than the noncomorbid form. However, although comorbidity is vitally important for efforts to understand, prevent, and treat emotional suffering, it is poorly understood. A promising starting point for explaining comorbidity is the relationship between generalized anxiety disorder (GAD) and major depressive disorder (MDD). Evidence that GAD and MDD share nearly all of their genetic risk hints at the existence of common processes that increase vulnerability for both disorders-processes which may represent potent targets for research and treatment. However, no one has yet attempted to determine just what is inherited by persons at risk for these disorders, nor what accounts for the presence of anxiety or depression in persons vulnerable to both. The central aim of this project is to evaluate 3 biobehavioral mechanisms that are hypothesized to contribute to GAD (threat sensitivity), MDD (reward responsiveness), or their comorbidity (perseverative thought). These candidate mechanisms will be studied in 4 groups-GAD, MDD, comorbid GAD-MDD, and healthy controls-that allow specific predictions to be tested about the relations of mechanisms to disorders. Mechanisms will be assessed on-line as they occur naturally in response to threat and reward experiences in the laboratory (using experimental paradigms) and in daily life (using ecological momentary assessment). Three studies will characterize the mechanisms in the disorder groups, address unresolved questions about the form of their disruption in GAD and MDD, and explore pathways through which they interact with the environment to maintain emotional disturbance. Discoveries resulting from this work are expected to inform interventions that, by targeting common as well as disorder-specific processes with increased precision, have the potential to improve outcomes for comorbid disorders. This would represent a significant step forward in addressing anxiety-mood comorbidity and its associated burden. PUBLIC HEALTH RELEVANCE: The burden of anxiety and depression is not distributed evenly in the population but is concentrated in a subset of individuals who suffer from multiple disorders. The current project seeks to isolate and characterize risk mechanisms that are specific to, and shared by, anxiety and depression. This represents an important step toward improved prediction, prevention, and treatment of comorbid disorders and their associated burden.